Quaternary ammonium haloethers



Pat nted Feb. 18, 1947 c QUATERNARY AMMONIUM HALOETHERS Clinton W. MacMullen and Herman A. Bruson, Philadelphia, Pa., assignors to Riihm & Haas Company, Philadelphia, Pa., a corporation of Delaware No Drawing. Application October I Serial No. 505,662

Claims.

This invention relates to aryl aliphatic ethers which contain an aromatic nucleus substituted by a quaternary ammonium methyl group and to processes for preparing such ethers. More particularly, this invention relates to ethers of the formula (ZCHz) nAIXAY wherein Z is a quaternary ammonium group, n is an integer having a value of one or two, Ar is a carbocyclic aromatic nucleus, X is oxygen or sulfur, A is an alkylene group the chain of which may be interrupted by oxygen or-sulfur, and Y is a polar group based upon the elements carbon, hydrogen, halogens, oxygen, and nitrogen, including such groups as OH,

O-alkyl, --O-aryl, CO-alkyl. CO-aryl, OCO-alkyl, OCO-aryl, COOH, COO- alkyl, CONHR', CONHR", -halogen,

-NRR", or -NRR"R"' anion, R'-R"' representing hydrogen or aliphatic, cycloaliphatic, arylaliphatic, heterocyclic, or aryl groups.

The quaternary ammonium methyl ethers of this invention may be prepared by reacting a tertiary amine with a halomethyl ether of the formula (CICI-Iz) nArXAY or by reacting an aminomethyl ether of the formula (Z'CHz) nArXAY wherein Z is a tertiary amino group with an alkylating or aralkylating agent.

As a halomethyl ether, there may be used any of the ethers described in the applications having Serial Numbers 415,034, 415,035, and 415,036, all filed September 2, 1941, now issued as United States Patents Nos. 2,291,526, 2,291,527, and 2,291,528, respectively, issued July 28, 1942, and in United States Patent No. 2,266,737, issued December 23, 1941.

Typical halomethyl aryl aliphatic ethers which are suitable as startin materials include such compounds as the following:

(ClCHz)nArOCHzCHzOH,where n has a value of one or two,

(CICHz) zCsHaSCI-IeCHzOCzHs (HalCHzMAflOCHzCHz) mO-alkyl, where m is an integer from one to ten or more and the alkyl group contains from one to eighteen carbon atoms,

In the above compounds the aromatic nucleus, designated Ar in generic terms and shown specifically as the phenyl group. may contain nuclear substituents such as alkyl, cycloalkyl, aryl, nitro, halogen, acyl, or other group which is sta ble under the conditions used in the preparation of the halomethyl ethers, that is, in the presence of a hydrogen halide and formaldehyde. This requirement excludes phenolic hydroxyl, amino, diazo and aldehyde groups. The aromatic nucleus may be mononuclearor polynuclear, as in benzene, naphthalene, phenanthrene, anthracene, diphenyl, etc.

As reactant with one of the above halomethyl aryl aliphatic ethers, there is used a secondary or tertiary amine to yield a tertiary amine or a quaternary ammonium salt. A product in the form of a tertiary amine may be converted by reaction with an alkylating or aralkylating agent into a quaternary ammonium salt. The reacting amines may be members of the aliphatic, arylaliphatic, cycloaliphatic, or aryl series or may contain substituents from two or more or these series. 'Iypica1"amines include dimethylamine,

I amaze;

diethylamine, dibutylamine, diethan'olamine, diallylamine, dimethallylamine, 'diisooctylamine. dodecylmethylamine, octadecylmethylamine, methylbenzylamine, dicyclohexylamine, methylaminobenzene, cyclic amines such as morpholine,

' piperidine, pyrrolidine, etc., trimethylamine, benz yldimethylamine, dodecyldimethylarhine, cyclohexyldimethylamine, dimethylaminobenzene, triamylamine, pyridine, etc. In fact, any secondary amines as morpholine and pyridine, the roups attached to the nitrogen are dior tri-valent {groups which form heterocycle-s with the nitrogen. v

The reaction between halomethyl arylaliphatic ether and secondary amine is carried out by reiacting said ether with anamine in the presence iof a base at a temperature between about-20 C. and about 250 C. If desired, the reaction may be performed in the presence of a solvent, such as ,dioxane, toluene, water, or the like. When sevjeral types of labile halogens are present in the ether, the reaction may be so conducted as to replace only one type or so as to replace all of 1 the halogens. If the reaction is carried out above about 100 C., the various labile halcgens are re- 1' placed by amine groups.

about 100 0., however, only the halogen of the halomethyl groups reacts. I In a similar way, the j reaction product may be varied in the case of the i ethers having -COOH, or -CCOR, or -000R 1 groups by variations in temperatures of reaction. Thus, in the lower range secondary amines react Between 20 C. and

only with the halogen of the halomethyl group,

Because of the difference in reactivity of the or with different such groups. Thus, the comexamples:

, act not-only with the halomethyl groupbut'also 5 with reactiveYgroups. I V

The quaternary ammonium ethers of this invention may be used as textile finishing agents,

disinfectants, bactericides, wetting agents, -detergents, insecticidal p ep drugs, fungicides, etc.

' The invention is illustrated by the following Example 1 I Seventy-three grams 1 of diethylamine was added to a cold solution of forty grams of sodium hydroxide in 120 grams of water. To this cold mixture was added with stirring seventy grams of chloromethyl o-cresoxy ethoxy ethyl chloride at 1 -6 to 1l C. The milky viscous mixture was stirred for twenty-five hours, during which time whereas in the upper temperature range there j occurs not only the reaction with the halomethyl 1 group but also reaction with the carboxyl group leading to (ii-substituted carboxylic amides and to alcohols.

different types of labile halogens, they may be 1 replaced with one type of amino nitrogen group 1 low 100 C. and this reacted above 100 C. to form V Tertiary amines prepared by reaction of halomethyl ether and secondary amine may be converted to the corresponding quaternary ammonium salt by reaction with such compounds as,

the dialkyl sulfates, as, for example, diethyl sulfate, alkyl halides as, for example, methyl iodide, bromide, or chloride, benzyl halides, esters, as,

for example, methyl formate, ethyl chloroacetatal or methyl-p-toluene sulfonate, alkyl halomethyl;

(Halogen CH2) nAIXAY Again by controlling conditions as to temperature of reaction in general below 100 C., only the halo- I methyl group may bereacted. More vigorous reaction conditions cause the tertiary amine to re the temperature rose to 27 C. The lower'aqueous layer was discarded, and the oil taken up in ben zene and washed twice with water. The crude amine was converted to its hydrochloride with hydrochloric acid, and the aqueous mixture steamdi'stilled to remove insoluble impurities. The residue stood a few days, and the slightly turbid aqueous solution wasdecanted from a few grams of heavy insoluble oil and clarified by agitation with an adsorbent clay. The clear amber filtrate was neutralized with sodium hydroxide solution, and the free amine liberated was taken upin benzene and washed. Thesolvent was distilled off in vacuo, and the residual oil clarified by stirring with 2.5 grams of activated charcoal. The forty-two grams of yellow oil obtained after filtration corresponded in composition to'diethylaminomethyl o-cresoxy ethoxy ethyl chloride having the formula refluxing ten grams of the diethylaminomethyl o-cresoxyethoxy ethyl chloride with eleven grams of ethyl bromide for One hour at 54 C. The excess ethyl bromide was then distilled out, leaving -a viscous paste which did not crystallize when cooled. The (c-chloroethoxy-ethoxy)-methylbenzyl triethyl ammonium bromide had the following formula Another quaternary ammoniumderivative was prepared by warming ten grams, of the diethylaminomethyl o-cresoxy ethoxy ethyl chloride with five grams of benzyl chloride for eight hours at 70 C. The '.(fi-chloroethoxy-ethoxy) -methylbenzyl diethyl benzyl ammonium chloride was a viscous'orange oil having the formula I CiHt' Q r I cim-N-cmcumwm)oczmocrnrci' 06115011, 01 A quaternary ammonium salt was prepared by heating six grams of .the diethylaminomethyl o-cresoxy ethoxy ethyl chloride with four grams of decyl chloromethyl ether for four and a half hours at C. The viscous red paste obtained was soluble in water with suds, and the product had the formula I CzHs\ I o onaocnrN-cmcrnncno00211400211401 I can i Example 2 A mixture of 156 grams of p-tert.-octyl phenoxy ethoxy ethyl chloride. thirty grams of paraformaldehyde, and 200 grams of ethylene dichloride was stirred and saturated with gaseous hydrogen chloride for seven hours at 50-53 C. The reac- -tion mixture was washed with ice water, dried with anhydrous sodium sulfate, filtered, and the solvent distilled off in vacuo, leaving 140 grams of clear amber oil.

This was crude chloromethyl p-tert.-octyl' phenoxy ethoxy ethyl chloride which was added during thirty-five minutes to a mixture of 360 grams of 25% dimethylamine solution and eighty grams of sodium hydroxide at 3-5 C., and the A quaternary ammonium salt was prepared by heating 7.5 grams of dimethylaminomethyl p-tert.-octyl phenoxy ethoxy ethyl chloride with three grams of methallyl chloride at 90 C. for five hours. The (B-chloroethoxy-ethoxy) -p-tert.- octyl-benzyl dimethyl methallyl ammonium chloride was obtained as a clear yellow viscous oil, soluble in water with suds, having the formula Forty-four grams of morpholine was mixed with a solution of twenty grams of sodium hydroxide in forty grams of water, and to this cold mixture was added, with stirring, 118 grams of chloromethyl p-tert.-octyl phenoxy ethoxy ethyl chloride during thirty minutes at 55-70 C. The turbid brown mixture was stirred for five and a half hours at 70-60 C. To the cooled reaction mixture was added 80 cc. of concentrated hydrochloric acid and 200 cc. of water, and the mixture steam-distilled to remove insoluble impurities. The residue was diluted with water and clarified by stirring twice with ten and twenty grams of activated charcoal, respectively. The aqueous solution was filtered, and neutralized to liberate the amine.

The amine was taken up in benzene and washed three times with water. The benzene was distilled off in vacuo, leaving 93 grams of viscous amber oil consisting of morpholinomethyl ptert.-octyl phenoxy ethoxy ethyl chloride which had the formula omen,

A quaternary ammonium salt was prepared by 6 octyl phenoxy ethoxy ethyl chloride with four grams of decyl chloromethyl other at 15 C. and.

stirring for ten minutes at 30-40 C. A very viscous, clear, amber oil was obtained, soluble in water with suds. The aqueous solution waspurifled by steam distillation and by agitation with an adsorbent clay. (fi-Chloroethoxy-ethoxw- (p-tert.-octyl)-benzyl decyl-oxymethyl morpholinium chloride had the following formula:

CBH17COH3OCLH4OOIHJC] I H2 C1uHzi0CH2NCI CH1- CH1 Another quaternary ammonium derivative was prepared by heating eight grams of morpholinomethyl p-tert.-octy1 phenoxy ethoxy ethyl chloride with 2.5 grams of ethyl chloroacetate at 200 C. for four hours. The viscous oil was extracted with hot water and the aqueous solution clarified with adsorbent clay and activated silica. The clear, amber, aqueous solution contained 8- chloroethoxy ethoxy) (p-tert.-octyl) benzyl carbethoxymethyl morpholinium chloride:

A quaternary ammonium salt was prepared by heating eight grams of morpholinomethyl p-tert.- octyl phenoxy ethoxy ethyl chloride with 3.5 grams of nitrobenzyl chloride at -185 C. for four hours. (B chloroethoxyethoxy) (p-tert.- octyl) -benzyl nitro-benzyl morpholinium chloride was a viscous dark oil, soluble in water with suds.

Example 4 Ninety-nine grams of chloromethyl p-tert.- octyl phenoxy ethoxy ethyl chloride at 31-40 C. was added during seventeen minutes to a cold mixture of fifty grams of dicyclohexylamine, eleven grams of water, and eleven grams of sodium hydroxide. The mixture was stirred for seven hours at '79-95 C., washed with water, and clarified by agitation with fifteen grams of active charcoal. The viscous yellow oil was dicyclohexylamino methyl p-tert.-cctyl phenoxy ethoxy ethyl chloride, having the formula A quaternary ammonium salt was prepared by heatin ten grams of dicyclohexylaminomethyl p-tert.-octyl phenoxy ethoxy ethyl chloride with three grams of ethyl chloroacetate for five hours at 140-180 C. The (p-chloroethoxy-ethoxy)- (p-tert.-octyl) benzyl dicyclohexyl carbethoxymethyl ammonium chloride was obtained as a yellow paste, having the formula A mixture of grams of dimethylaminomethyl p-tert.-octyl phenoxy ethoxy ethyl chloride (prepared as in Example 2), 180 grams of 25% dimethylamine, 1000 grams of water, and

' mixing eight grams tert.-octyl phenoxy ;with 5.6 grams of methyl iodide; An exothermic reaction took place, and the mixture was cooled. The solid mass was recrystallized from ethylene CH:\ CH: NClIaCaHflCaHn) 021140 C2H4N CH. CH5

A quaternary ammonium salt was prepared by of dimethylaminomethyl pethoxy ethyl dimethylamine dichloride and petroleum ether (90-100 C.).

The dimethylaminomethyl p-tert.-octyl phenoxy ethoxy ethyl dimethylamine obtained as a colorless crystalline solid, soluble in water, and having the formula di-methiodide was A quaternary ammonium salt was also prepared by mixing eight grams of dimethylaminomethyl p-tert.-octyl phenoxy methylamine with six grams of diethyl sulfate.

1 An exothermic reaction occurred, yielding a vis- 1 cous pastewhen cooled, which was clearly soluble in water with suds. The di-quaternary salt had the following formula CzHs /C2Ha CHrNCHaCaHflQBHn) 0 021140 cram-cm on; I s ogo 0,115 out Example 6 Three hundred sixty grams of 25% dimethylamine solution was added to thirty-two grams of di-(chloromethyl) phenoxy ethyl chloride and hydroxide was stirred and A quaternary ammonium derivative was prepared by stirring a mixture of forty grams of dl- (morpholinomethyl) phenoxy ethoxy ethyl chlo-' ride, twenty-two grams of benzyl chloride, and

s The reaction mixture was steam-distilled to remove water-insoluble im- 125 grams of toluene at 80-90 C. for four hours..

purities. A small amount of heavy brown oil layer was separated off on standing, and the quaternary ammonium salt was obtained as a I clear aqueous solution.

ethoxy ethyl di- 1 the mixture stirred and heated for fourteen hours 1 I at 41-69 C. A solution of twelve grams of so- 120 cc. of water was added dium hydroxide in and the mixturefstirred for five hours. The mixture was filtered, and the filtrate extracted four times with benzene. The benzene 'was distilled off and the residual oil distilled in vacuo. The yellow oil boiling at HIP-140 C./l mm. was di-(dimethylamino-methyDphenoxy ethylene, having the formula (CHahNCHzCeHaO CHI-CH:

- CHzN(CHs)z j Example? Sixty grams of di-(chloromethyDphenoxy ethoxy ethyl chloride was added to a cold mixture of forty-eight grams of Water, sixteen grams of sodium hydroxide, and thirty-five grams of morpholine at 25-45 C. and the mixture stirred for six hours at 95 C. The oil layer was separated, washed, taken up in benzene and dried, and the benzene distilled oil? in vacuo. The clear amber oil obtained was di-(morpholino-methyl) phenoxy ethoxy ethyl chloride having the for-j mula I CHzCHa o Ncmctnao 0,1140 clulcncnm o 7 CHLCH: CHaCH:

A quaternary ammonium salt was prepared by warming four grams of di-(morpholinomethyl) phenoxy ethoxy ethyl chloride with two grams of chloromethyl o-cresoxy ethyl chloride,

at C. for three hours. The mixture became very viscous and, when the mixture was cooled, the quaternary ammonium salt was obtained as a solid which was soluble in water.

Example 8 One hundred eighty grams of chloromethyl phenoxy ethyl acetate, ClCHzCsH4OC2I-l4OCOCH3 (containing also some di-chloromethyl phenoxy ethyl acetate), 1080 grams of 25% dimethylamine, grams of water, and 80 grams of sodium hydroxide were stirred in an autoclave and heated for five hours at l35-165 C. The mixture cooled overnight, and the viscous sticky oil was separated from the aqueous layer with the aid of benzene. The solvent was distilled oil and the residual oil distilled in vacuo. ether alcohol, formed by substitution of the halogen and ammonolysis of the ester groups, was obtained as a viscous oil, boiling at 133-165 C./1-2 mm. The product was a mixture of dimethylaminomethyl phenoxy ethanol NCHzColLO C2H40H and di-(dimethylaminomethyl) phenoxy ethanol NCHzCaHSO 0211.011 CH3 CHs HzN Example 9 A mixture of sixty-nine grams of phenyl hydroxyethyl ether, CsH5OC2I-I4OH, sixty grams of paraformaldehyde, and 200 cc. of petroleum ether was stirred and saturated with hydrogen chloride for six hours at 3040 C. .The crude oil was washed With water, dried with anhydrous so filtered, and the solvent distilled dium sulfate, ofi under reduced pressure.

Ninety-six grams of the chloromethyl derivative thus obtained was added to a cold mixture of 540 grams of 25% dimethylamine solution and grams of sodium hydroxide during twentyminutes at 4-20 C., and the mixture stirred for twenty-three hours at 20-30 C. The oil was separated, taken up in benzene, washed with water, dried with anhydrous sodium sulfate, and

distilled in vacuo. The dimethylaminomethyl 'derivative of phenoxy ethanol was obtained as a clear, pale yellow'oil, boiling at l60 C./2

mm. The product was a mixture of the monoconcentrated, and

The amino and di-dimethylaminomethyl derivative having the formulas A quaternary ammonium salt was prepared by heating four grams of the dimethylaminomethyl derivative of phenoxy ethanol obtained above and three grams of n-hexyl bromide for a half hour at 95 C. The hot viscous reaction mixture was cooled to a sticky solid, which was soluble in water.

Ezample A mixture of sixty-two grams of phenoxy acetone, eighty-one grams of 37% formaldehyde, and three hundred grams of dioxane was stirred and saturated with hydrogen chloride for seven and one-half hours at 10-30 C. The clear dark brown solution was poured into a large volume of ice water, the oil extracted with benzene, washed, and dried.

The benzene solution of di-(chloromethyl) phenoxy acetone, containing also some chloromethyl phenoxy acetone, was added to a cold mix ture of 180'grams of 25% dimethylamine solution and forty grams of sodium hydroxide at 10- C., and the heterogeneous brown mixture stirred for fifteen hours at 20-30 C. The benzene layer was distilled in vacuo, and the dimethylaminomethyl derivative was obtained as a clear yellow oil boiling at 120-155 C./2 mm., sparingly soluble in water, but clearly soluble in dilute hydrochloric acid. The product was di- (dimethylaminomethyl) phenoxy acetone containing also some dimethylaminomethyl phenoxy acetone (CH3) 2NCH2C6'H4OCH2COCH3 Example 11 A mixture of 138 grams of phenyl hydroxyethyl ether, CsH5OC2H4OH, 120 grams of paraformaldehyde, and three hundred grams of dioxane was stirred and saturated with hydrogen chloride for fifteen hours at 5060 C. and for four hours at 10-20. C. The reaction mixture was poured into one liter of ice water, the oil layer separated and taken up in 300 cc. of benzene, dried with anhydrous sodium sulfate and filtered. Half of the benzene solution was stripped in vacuo to give a clear amber oil which was di-chloromethyl phenoxy ethanol, containing also some chloromethyl phenoxy ethanol.

Two hundred forty-five grams of the benzene solution of the chloromethyl derivative thus obtained was added to a, cold mixture of 540 grams of 25% of sodium hydroxide during fifteen minutes at 0-10 C. and the turbid milky solution stirred for twenty-five hours at 1020 C. The oil layer was separated, taken up in benzene, washed with water, dried, and distilled in vacuo. A clear,

colorless oil was obtained, boiling at 150-170 C./2 mm., which was di-dimethylaminomethyl phenoxy ethanol, containing also some dimethylaminomethyl phenoxy ethanol.

dimethylamine solution and 120 grams Example 12 CHrC'Hz CHzCH; O /NCH|CtHOCH:CON /O CHzCH: CHICK:

containing also some di-morpholinomethylphenoxy acetyl morpholine:

CHzCH: CHzCHz O NCHzCaHsO CHzC ON O cmcni Ha CH:CH:

C CH: {'1 CH2 Quaternary salts may be formed therefrom by reacting with an alkylating or aralkylating agent as in previous examples.

Example 13 ter. It was a product of the formula Example 14 A mixture was made with eighty parts of pyri dine and 150 parts of chloromethyl phenoxyethoxyethyl chloride and heated gradually up to about C. The resulting product was soluble in water and showed the typical behavior of quaternary salts.

Example 15 A mixture was prepared from 200 parts of benzyl dimethylamine and 295 parts of chloromethyl cresoxyethoxyethoxyethyl chloride and the temperature thereof carried to about 100 C. A water-soluble product was obtained.

Example 16 Three hundred eighty-two grams of an emulsion containing 21% of chloromethyl p-tert.-octyl phenoxy-ethoxy-ethoxy-ethyl dodecyl ether,

was added to a cold mixture of one hundred grams of water, twenty grams of soduim hydroxide, and one hundred grams of monoisopropyl amine, and the mixture stirred for fifteen hours at 20-25 C. Then 20 cc. of 25% sodium hydroxide solution was added and stirring continued for live hours. The oil layer was separated,

The mixture stood several days and was 2 11 taken up in benzene. washed, dried, and distilled invacuo. The clear red oil, boiling at 150 250 C./2 -mm-., was isopropylamino methyl ptert.-octyl phenoxy-ethoxy-ethoxy ethyl lauryl ether 4 H CH3 i H'oNcH,c.moo,n.0oiH.ommoom CHa aHn- ;This amine is readily converted to the quaternary ammonium derivative by reacting it with an alkylating agent .such as benzyl chloride or bromide. V f 1 ,1 According to this invention, compounds of the general formula a I (Halogen-CHzMArXAY react with secondary amines to form tertiary amines of the formula which are then converted to the corresponding quaternary amino compound by the addition thereto of an alkylating or aralkylating agent.

. 5 Alternatively, the compound 3 (Halogen CH2) nAIXAY may be reacted with any tertiary amine, NR'R' IR! I I where R, R",-and R' are aliphatic, alicyclic,

aralkyl, heterocyclic, or aryl groups.

The quaternary ammonium group, Z, in the general formula (ZCI-IzMArXAY imay take the forms 4 'N b d d d where a, b, and c are monovalent groups, e is a I saturated divalent group,-f is an unsaturated trivalent group,'and dis an anion.

This application isa continuation-in-part of application Seria1 No. 445,452, filed June 2, 1942. It is particularly directed to quaternary ammonium compounds of the formula (ZCHz) nAIXA halogen prepared from halomethyl ethers of the general formula I (Halogen'CHz) nAl'XAZ halogen We claim Y v 1. Compounds of the formula (zcnmA'roa halogen I 12 wherein Z represents the group p 1 'Rl anion wherein R1, taken individually represents monovalent, aliphatic, cyclohexyl, and benzyl groups,

R2, taken individually, represents alkyl and cyclohexyl groups, R3, taken individually, represents monovalent aliphatic groups, R1 and R2, taken together, represent divalent saturated aliphatic hydrocarbon and ether chains which form a heterocycle with the nitrogen, and R1, R2, and

R3, taken together; represent a trivalent unsaturated hydrocarbon chain which forms a heterocycle with the nitrogen, 11. is an integer having a value from one to two, inclusive, Ar is a carbocyclic aromatic grou and A'is selected from a member of the class consisting of alkylene groups and alkylene groups the chain of which is interrupted by oxygen.

2. Compounds of the formula 7 CH: I

CHs N-CH: phenyl 0A halogen Celia CH2 1 wherein A isan alkylene group which is inter- 1 rupted by oxygen.

cLrrrroNw. MACMULLEN. HERMAN A.- BRUSON.

REFERENCES CITED The following references are of record in th.

file of this patent: I

, UNITED STATES PATENTS Number Name Date 2,291,528 Bruson V July 28, 1942 2,336,465

Buck Dec. 14, 1943 

